Mice immunized with purified recombinant envelope glycoprotein from a variety of HIV-1 isolates were studied to determine the number, specificity and crossreactivity of B cells producing antibodies against gpl2O. Results indicate that immunization with gpl2O from a single isolate of HIV-1 activates B cells reactive with that isolate but not with gpl2Os from other HIV-1 strains. In contrast, sequentially immunizing mice with different gpl2O isolates induced the preferential expansion of highly cross-reactive B cells. These findings may be useful in designing an immunization protocol to optimize the stimulation of broadly protective anti-HIV antibodies. ii) Mice inoculated with the LP-BM5 type C retrovirus develop murine AIDS, a syndrome similar to human AIDS. We have shown that the humoral manifestations of LP-BM5 infection occur in three non-discrete stages marked by i) polyclonal B cell activation, ii) hypergammaglobulinemia and iii) generalized immunosuppression. We are using the MAIDS model to study the efficacy of X-irradiation and bone-marrow reconstitution combined with AZT therapy on disease progression. Mice with MAIDS will also be studied for the development of autoimmune cardiomyopathy following infection with Coxsackie B virus. iii) Abnormal B cell activation is characteristic of retrovirus induced diseases, such as AIDS, and autoimmune diseases, such as systemic lupus erythematosus. Using, a sensitive and specific ELISA spot assay, we have been studying the number and antigenic specificity of those B cells actively secreting Ig in vivo in patients with these diseases. Results indicate that two processes - polyclonal activation .and (auto)antigen specific immune stimulation - combine to induce the humoral abnormalities found in both AIDS and SLE. This work is also providing considerable insight into the degree to which HIV-1 specific B cells are activated in patients with ARC and AIDS.